ERK1 phosphorylates Nanog to regulate protein stability and stem cell self-renewal

作者：Kim Sung Hyun; Kim Myoung Ok; Cho Yong Yeon; Yao Ke; Kim Dong Joon; Jeong Chul Ho; Yu Dong Hoon; Bae Ki Beom; Cho Eun Jin; Jung Sung Keun; Lee Mee Hyun; Chen Hanyong; Kim Jae Young; Bode Ann M; Dong Zigang^*

来源：Stem Cell Research, 2014, 13(1): 1-11.

DOI：10.1016/j.scr.2014.04.001

Nanog regulates human and mouse embryonic stem (ES) cell self-renewal activity. Activation of ERKs signaling negatively regulates ES cell self-renewal and induces differentiation, but the mechanisms are not understood. We found that ERK1 binds and phosphorylates Nanog. Activation of MEK/ERKs signaling and phosphorylation of Nanog inhibit Nanog transactivation, inducing ES cell differentiation. Conversely, suppression of MEK/ERKs signaling enhances Nanog transactivation to inhibit ES cell differentiation. We observed that phosphorylation of Nanog by ERK1 decreases Nanog stability through ubiquitination-mediated protein degradation. Further, we found that this phosphorylation induces binding of FBXW8 with Nanog to reduce Nanog protein stability. Overall, our results demonstrated that ERKs-mediated Nanog phosphorylation plays an important role in self-renewal of ES cells through FBXW8-mediated Nanog protein stability.

• 出版日期2014-7